DESCRIPTION: The goal of this proposal is to understand the effect of a deficiency of Se and vitamin E on the host's ability to respond to infection with CVB3. Infection with CVB3 commonly occurs in childhood and often is asymptomatic; however, CVB3 can cause more serious disease, such as encephalitis, meningitis, or paralysis. Results from the investigator's laboratory demonstrate that mice fed diets deficient in either Se or vitamin E develop much more severe myocarditis from CVB3 than mice fed diets adequate in these antioxidant nutrients. Of particular interest is that a benign strain of CVB3, which does not cause myocarditis in mice fed an adequate diet, does cause myocarditis in deficient mice. Based on preliminary evidence, the investigator hypothesizes that oxidative stress induced by a deficiency of either Se or vitamin E affects both the immune system and cardiac cells such that a normally benign virus becomes virulent, and that the enhanced virulence is due to a mutation in the viral genome itself. The specific aims of the proposal are: (1) to compare the immune responses of CVB3-infected mice fed adequate, Se-deficient, or vitamin E-deficient diets, (2) to determine the direct impact of Se or vitamin E deficiency on cardiac cells and their resistance to viral replication, (3) to determine if high levels of Se or vitamin E supplementation promote resistance to CVB3-induced infection and/or pathology, and (4) to determine the nucleic acid sequences of viruses obtained from nutritionally deficient hosts. The study will provide information on the role of dietary antioxidant nutrients during infection with CVB3 and may have implications for other viral infections.